Journal of Hepatology
Volume 58, Issue 5, May 2013, Pages 904–910
Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats
Marco Di Pascoli†,
Joan Carles García-PagánCorresponding author contact information, E-mail the corresponding author
Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Ciberehd, University of Barcelona, Spain
http://dx.doi.org/10.1016/j.jhep.2012.12.012, How to Cite or Link Using DOI
Background & Aims
Resveratrol, a polyphenol found in a variety of fruits, exerts a wide range of beneficial effects on the endothelium, regulates multiple vasoactive substances and decreases oxidative stress, factors involved in the pathophysiology of portal hypertension. Our study aimed at evaluating the effects of resveratrol on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl4 cirrhotic rats.
Resveratrol (10 and 20 mg/kg/day) or its vehicle was administered to cirrhotic rats for two weeks and hepatic and systemic hemodynamics were measured. Moreover, we evaluated endothelial function by dose-relaxation curves to acetylcholine, hepatic NO bioavailability and TXA2 production. We also evaluated liver fibrosis by Sirius Red staining of liver sections, collagen-1, NFκB, TGFβ mRNA expression, and desmin and α-smooth muscle actin (α-SMA) protein expression, as a surrogate of hepatic stellate cell activation.
Resveratrol administration significantly decreased portal pressure compared to vehicle (12.1 ± 0.9 vs. 14.3 ± 2.2 mmHg; p <0.05) without significant changes in systemic hemodynamics. Reduction in portal pressure was associated with an improved vasodilatory response to acetylcholine, with decreased TXA2 production, increased endothelial NO, and with a significant reduction in liver fibrosis. The decrease in hepatic fibrosis was associated with a reduced collagen-1, TGFβ, NFκB mRNA expression and desmin and α-SMA protein expression.
Resveratrol administration reduces portal pressure, hepatic stellate cell activation and liver fibrosis, and improves hepatic endothelial dysfunction in cirrhotic rats, suggesting it may be a useful dietary supplement in the treatment of portal hypertension in patients with cirrhosis.
NO, nitric oxide;
eNOS, endothelial nitric oxide synthase;
CCl4, carbon tetrachloride;
MAP, mmHg, mean arterial pressure;
PP, mmHg, portal pressure;
PBF, ml min−1, portal blood flow;
SMABF, ml min−1, superior mesenteric artery blood flow;
TXB2, thromboxane B2;
View the MathML sourceO2-, superoxide;
cGMP, cyclic guanosine monophosphate;
P-eNOS, phosphorylated eNOS;
α-SMA, α smooth muscle actin